Our previous application set up the hypothesis that certain forms of periodontitis were specific infections due to proportional overgrowth of anaerobic species, such as spirochetes and B. gingivalis. We have conducted double blind studies using metronidazole, which showed that patients who received tooth surface debridement and one week of systemic metronidazole required significantly less periodontal surgery than the control patients. In the current proposal we seek to determine whether periodontal surgery can be reduced and/or eliminated by root surface debridement plus the usage of drugs directed against periodontopathic organisms and/or the host's inflammatory response. The drugs to be evaluated will be metronidazole and tetracycline, each taken systemically for a two-week period after the scaling and root planing is completed. Teeth that are refractory to this regimen and still require some form of periodontal surgery will have ethylcellulose films containing either metronidazole or chlorhexidine placed within their pockets for one week or more. These films are fabricated so that the drug is slowly released over a 3- to 10-day period. The reduction in surgical needs will be judged by clinical criteria and will be verified by standardize radiographs and bacteriological parameters. Patients seen at the annual recall visit will receive either metronidazole or tetracycline in a double blind design to determine the prophylactic value of periodic antimicrobial treatment during the maintenance phase. Bacteriological parameters will be obtained throughout the study period. In a related investigation, patients who have an anaerobic periodontal infection will receive metronidazole or placebo under supervision. The serum and saliva levels of metronidazole will be compared with the changes in levels and proportions of spirochetes in the plaque and with the ability of the plaque to hydrolyze the trypsin substrate BANA. In this way we hope to determine whether patient compliance in the systemic usage of metronidazole can be measured by changes in the plaque levels and/or proportions of spirochetes or in the ability of the plaque to hydrolyze BANA. Finally, we will develop and deploy slow release ethylcellulose film systems for the delivery of nonsteroidal anti-inflammatory agents, such as indomethacin to the periodontal pocket either alone or in combination with metronidazole or chlorhexidine.